(214b) Effect of Freezing Rate and Geometry on Protein Particle Formation and Storage Stability | AIChE

(214b) Effect of Freezing Rate and Geometry on Protein Particle Formation and Storage Stability

Authors 

Rodrigues, M. A. - Presenter, University of Texas at Austin
Miller, M. A. - Presenter, University of Texas at Austin


A variety of freezing processes including spray freeze drying, thin film freezing and bulk freezing are utilized for producing protein particles for drug delivery. Thin film freezing (TFF) enables freezing at considerably fast cooling rates (of ~102 K/s), without exposing the proteins to large gas-liquid interfaces which can otherwise lead to unfolding and aggregation. The cooling rates experienced in the TFF process permit the formation of an ice template, where thin liquid channels formed between the ice domains produce high freezing rates. Upon lyophilization of such ice structures, fine protein particles with sizes on the order of a few 100 nm have been harvested. The objective of this work was to relate the protein morphology to the freezing rates for solutions with varying heats of solution and freezing points. The particle morphology was analyzed by scanning electron microscopy, and the size distribution was measured by laser light scattering and aerodynamic time of flight.

Freezing processes are also of interest in storage stability. Freezing processes can lead to losses in protein stability as a result of exposure to air-water and ice-water interfaces and cold denaturation as well as freeze-concentration. We report how the freezing rate and geometry influence ice formation, freeze-concentration and protein stability in the frozen state. Freezing temperature profiles and ice front velocities were measure to understand the stresses experienced by the protein and how they influence protein stability.